The goal of the proposed research is to develop an assay to identify potential antiviral and anticancer compounds. The assay is based on the activity of the cellular enzyme PKR (Protein Kinase RNA-activated). PKR is induced by interferon and requires double-stranded RNA for activation. Activated PKR inhibits translation. By inhibiting translation the cell stops viral replication since viruses are dependent on host translation. Some viruses (adenovirus, vaccinia virus, rotavirus, reovirus, poliovirus, influenza, and possibly HIV) have evolved mechanisms to counteract this anti viral system by inhibiting PKR. The fact that many pathogenic viruses have inhibitors of PKR suggests that inhibition of this enzyme is important for viral replication. In addition to its anti viral effects, PKR may also function as a suppresser of cell proliferation and tumor formation. Though tightly regulated, PKR apparently must be expressed and activated at times during the cell cycle. In this context, activators of PKR may be useful as antitumorigenic compounds, since activation could inhibit translation, perhaps leading to growth suppression of the tumor. The assay described here is a simple assay of PKR activity that can be adapted to identify activators of PKR, or to identify compounds that block viral inhibitors of PKR.